Alkyl (n-phenylsulfonyloxy) carbamates

ABSTRACT

Substituted (N-p-arylsulfonyloxy)carbamates are disclosed. These compounds are used as starting materials in the preparation of 1,4-benzodiazepin-2-ones.

United States Patent [191 Hellerbach et al.

[ Dec. 10, 1974 ALKYL (N-PHENYLSULFONYLOXY) CARBAMATES [75] Inventors:Joseph Hellerbach, Basel,

Switzerland; Armin Walser, West Caldwell, N.J.; Hermann Bretschneider,lnnsbruck, Austria; Werner Rudolph, Lorrach, Germany [73] Assignee:Hoffman-La Roche Inc., Nutley,

22 Filed: June 25,1973

21 Appl. No.: 373,070

Related U.S. Application Data [62] Division of Ser. No. 111,731, Feb. 1,1971, Pat. No.

[30] Foreign Application Priority Data Feb. 11, 1970 Switzerland 1956/70[52] U.S. Cl. 260/470 OTHER PUBLlCATlONS Steinberg et al., J. Org. Chem.21, 660, (1966).

March, Adv. Organic Chemistry, McGraw-Hill, (1968), N.Y., PP. 373.

Primary ExaminerLorraine A. Weinberger Assistant ExaminerJohn F.Terapane Attorney, Agent, or FirmSamuel L. Welt; Bernard S. Leon; FrankP. Hoffman [57] ABSTRACT Substituted (N-p-arylsulfonyloxy)carbamates aredisclosed. These compounds are used as starting materials in thepreparation of l,4-benzodiazepin-2-ones.

4 Claims, No Drawings ALKYL (N -PHENYLSULFONYLOXY) CARBAMATES Thepresent application is a divisional of application Ser. No. 111,731filed Feb. 1, 1971 which is now US. Pat. No. 3,772,271 issued Nov. 11,1973.

DESCRIPTION OF THE INVENTION NHCOOR;

NC c:

wherein R signifies halogen or nitro; R signifies hydrogen or halogen; Rsignifies hydrogen, lower alkyl or aryl; R signifies lower alkyl, andthe pharrnaceutically acceptable acid addition salts thereof.-

As used herein, the term lower alkyl" denotes straight or branched chainhydrocarbon groups containing from l-7 carbon atoms, preferably l-4carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, and the like.The expression aryl denotes a phenyl residue or a halo or loweralkyl-substituted phenyl residue such as o-tolyl, m-tolyl, p-tolyl,o-chlorophenyl, mfluorophenyl, p-bromophenyl, and the like. The termhalogen denotes all four forms thereof, i.e., fluorine, chlorine,bromine and iodine, unless indicated otherwise.

Among the preferred compounds falling within the scope of formula Iabove are those wherein the R substituent is substituted at the7-position of the benzodiazepine moiety. Likewise preferred are thosecompounds of formula I wherein R is located in the orthoposition of theS-phenyl ring if it represents halogen. Further preferred are thecompounds of formula I wherein the R substituent is chlorineor nitro andis located in the 7-position of the benzodiazepine moiety; the Rsubstituent is hydrogen, chlorine or fluorine and is located in the2'-position of the benzoidiazepine moiety, and the R substituent ishydrogen, methyl or phenyl, i.e., compounds of the formula wherein R isas above; R signifies chlorine or nitro; R signifies hydrogen, chlorineor fluorine; R signifies hydrogen, methyl or phenyl and thepharrnaceutically acceptable acid addition salts thereof.

Most preferred of the compounds of formula I above are:

EthyI-[(2,3-dihydro-7-nitro-2-oxo-5-phenyll l-ll ,4- benzodiazepinl -yl)methyl carbamate;

Ethyl- 7-chloro-2,3-dihydro-2-oxo-5-phenyl- 1H- 1 ,4-benzodiazepinl -yl)methyl ]carbamate;

Ethyl- [7-chloro-5-(2-chlorophenyl)-2,3-dihydro-2- oxol I-l- 1,4-benzodiazepinl -yl methyl carbamate;

Ethyl-[a-( 7-chloro2,3-dihydro-2-oxo-5-phenyll H- l ,4-benzodiazepin- 1-yI )benzyl carbamate;

Ethy1-[ l-( 7-chloro-2,3-dihydro-2-oxo-5-phenyll H l ,4-benzodiazepin- 1-yl )ethyl ]carbamate.

The novel compounds of formula I above can be prepared following avariety of procedures.

A. In one process aspect of the present invention, the compounds offormula I may be prepared by reacting a compound of the formula whereinR and R are as described above, with a compound of the formula wherein Rand R are as described above and R signifieslower alkyl or aryl, in thepresence of a base.

The reaction between the compounds of formulae II and III above isexpediently effected in the presence of an anhydrous polar aproticsolvent such as dimethylfonnamide and like solvents. Preferred bases forthe purposes of this process aspect include tertiary aliphatic aminessuch as triethylamine. Although temperature and pressure are notcritical to this process aspect, it is preferable to effect the reactionat elevated temperatures, most preferably, at the reflux temperature ofthe reaction medium.

The R substituent in the compounds of formula III can be, for example,methyl, ethyl, phenyl, p-

bromophenyl, or p-tolyl. Examples of compounds of formula III suitablefor the process include ethyl (N-methyl-N-p-toluenesulfonyloxy)carbamate, ethyl (N-benzyl-N-p-toluenesulfonyloxy)carbamate or ethyl (N-ethyl-N-p-toluenesulfonyloxy)carbamate.

The compounds of formula III above used as starting materials for thisprocess aspect are new substances, and as such form a part of thepresent invention. These compounds of formula 111 can be prepared byacylating a compoundof the general formula Oil R3 1v wherein R and R areas described above, with a reactive derivative of a sulfonic acid of thegeneral formula and the like is, for example, used as the compound offormula IV. The reaction conditions largely depend on the nature of thesulfonic acid derivative employed as the acylating agent. Thus, forexample, the acylation is with advantage carried out in pyridine when anacid halide is used as the acylating agent.

The compounds of formula III above can be used not only for the purposesof this process aspect of the invention, but in addition asintermediates in many phases of preparative organic chemistry. Forexample, these compounds can be used generally for N- substitution ofprimary and secondary amides with the residue -CH(R )NHCO0R wherein Rand R are as described above. In reacting the compound of formula IIIwith the amide to be substituted, the reaction is effected in thepresence of a base. This reaction is expediently effected in thepresence of an anhydrous polar aprotic solvent such as dimethylformamideand like solvents. Preferred bases for this purpose include tertiaryaliphatic amines such as triethylamine. Although temperature andpressure are not critical to the successful performance of thisreaction, it is preferable to effect the reaction at elevatedtemperatures, most preferably at the reflux temperature of the reactionmedium.

The compounds of the above formula IV are known or are accessibleaccording to known processes, for example, by reaction of thecorresponding hydroxylamines of the formula wherein R is asdescribedabove, with a lower alkyl ester of chloroformic acid.

B. In a second process aspect of the present invention, the compounds offormula I can be prepared by cycli zing a compound of the generalformula VII wherein R R R and R are as described above.

The cyclization of the compound of formula VII is readily effected inthe presence of an inert organic solvent. Suitable solvents for thispurpose include lower alkanols, such as methanol, ethanol, and the like,ethers such as dioxane, tetrahydrofuran, and the like, amides such asdimethylformamide, and the like. The cyclization reaction can also beeffected in an aqueous medium. In a preferred embodiment of this processaspect, a solution, especially an aqueous solution of a suitable acidaddition salt (i.e., the hydrochloride) of the compound of formula VIIis made neutral to alkaline, for example, by addition of sodiumcarbonate solution, whereupon spontaneous cyclization to thecorresponding derivative of formula I is effected.

Examples of compounds of formula VII suitable for this process aspectinclude 2-amino-N- (ethoxycarbonylamino )methyl ]-2-benzoyl-4-chloroacetanilide, Z-amino-N- [(ethoxycarbonylamino)methyl-Z'-benzoyl-4-nitroacetanilide, 2-amino-N- [(ethoxycarbonylamino )methyl 1-4'-chloro-2 ochlorobenzoyl)-acetanilide, Z-amino-N-[a-(ethoxycarbonylaminmbenzyl]-2"benzoyl-4'- chloroacetanilide, 2-amino-N-[l- (ethoxycarbonylamino)ethyl]-2'-benzoyl-4'- chloroacetanilide and thelike.

The compounds of formula'VII above used as starting materials in thisprocess aspect of the present invention can be prepared by reacting acompound of the formula VIII wherein R, and R are as described above,and X signifies any suitable protecting group, with a compound offormula III above in the presence of a base and subsequently splittingoff the protecting group. A suitable protecting group for this purposeis a carbobenzoxy group which can be removed hydrogenolytically, forexample, by hydrogen in the presence of a palladium catalyst. If theremoval of the protecting group is effected in an acidic medium thereresults the acid addition derivative of the compound of formula VII. Ifremoval of the protecting group is effected in neutral or alkalinemedium, cyclization of the formula VII compound occurs spontaneouslyresulting in the corresponding compound of formula I. I

The reaction betweenthe compounds of formulae III and VIII isexpediently effected in the presence of a base and an anhydrous polaraprotic solvent such as dimethylformamide and like solvents. Suitablebases for this purpose include tertiary aliphatic amines such astriethylamine. It is preferable to conduct this reaction at elevatedtemperatures, most preferably at the reflux temperature of the reactionmedium.

The benzodiazepine derivatives of formulal are basic in nature and canbe converted into their pharmaceutically acceptable acid addition saltsby reaction with organic or inorganic acids. Examples of acids whichform pharrnaceutically acceptable salts are hydrogen chloride, hydrogenbromide, sulfuric acid, acetic acid, maleic acid, methanesulfonic acid,p-toluenesulfonic acid, and the like.

The compounds of formula 1 above exhibit sedative, anticonvulsantand-muscle relaxant properties. The anti-convulsant activity of thesecompounds may be demonstrated by employing standard techniques. Forexample, the anti-convulsant activity can be shown by subjecting mice towhich a compound of formula I or a salt thereof has been administered tothe pentamethylene tetrazole test following the method disclosed byOrloff [Proc. Soc. Exptl. Biol. Med. 70, 254-257 (1949)]. The resultsare stated as APR 2.0, which indicates that dosage (in mg/kg. p.o.) ofan anticonvulsant which brings about doublethe pentamethylene tetrazoleconsumption compared with the untreated control group.

mice which are under the influence of a muscle relaxant or sedativecompound to hold on to a slowly rotating rod. The rod used has adiameter of 30 mm. and rolutions, suspensions or emulsions). They may besterilized and/or contain additives such as preserving, stabilizing,wetting or emulsifying agents, salts for varying the osmotic pressure orbuffers. They can also contain yet other therapeutically valuablesubstances. The dosage follows individual requirements, but a dosage of0.1 mg/kg. to 5 mg/kg. per day is preferred.

The following Examples illustrate the invention. All temperatures arestated in degrees Centrigrade.

EXAMPLE I A mixture of 14 g. of l,3-dihydro-7-nitro-5-phenyl- 2H- 1,4-benzodiazepin-2-one, 20 g. of ethyl (N-methyl-N-p-toluenesulphonyloxy)carbamate, 50 ml. of triethylamine and 50 ml. ofdimethylformamide is boiled under reflux for 3 hours. The mixture isthereupon evaporated, initially in vacuum and then under high vacuum,and the residue is partitioned between methylene chloride and l0 percentsodium bicarbonate solution. The methylene chloride phase is separatedoff, washed with sodium carbonate solution and water, dried over sodiumsulfate and evaporated. Chromatography of the residue on 500 g. ofsilica gel with 20 percent ethyl acetate in methylene chloride yields,after tates at a speed of two rotations per minute. For thecrystallization from methylene chloride-ether, ethyl test, those miceare selected which prior to receiving2,3-dihydro-7-nitro-2-oxo-5-phenyl-lH-l,4- medication could hold on tothe rotating rod for at least benzodiazepin-l yl)methyl]carba mate whichmelts at 2 minutes. After the mice are selected, these animals 157-l60after recrystallization from methanol.

are given the compounds to be tested in various dos- Th th l(N-methyl-N-p-toluenesulphonyloxy)carages- The animals are then Placedon the rotating rod bamate used as the starting material can be manufac-30 minutes after administration of the compounds. The t d a follows;

time for which each of the mice can stay on the rotating A l ti n f 38g, of p-toluenesulphonyl chloride in rod is calculated. The dosage whichcauses a 50 per- 100 m1, f pyridine is added dropwise with ice-coolingcent reduction of the time the animals hold on to the nd onstantstirring to a solution of 24 g. of N-methylrod is designated as th -soN-carbethoxyhydroxylamine in 60 ml. of pyridine, in

The toxicity of the compounds of formula I is doing which the reactiontemperature should not extrated y the indication of the -soceed 5. Themixture is subsequently stirred for a fur- The following table setsforth the results of the testing h 4-5 hours at room temperature, themajor part of for representative compounds of formula I. These test thpy idi i removed on the rotary evaporator at a reports relate to thefollowing compounds: temperature of and the residue is taken up with 100Ethyl y -P H- rnl. of water and 300ml. of ether. The aqueous phase1i4'behzodiazepih'l-ynmethyllcarbamate; is separated off; the organicphase is washed 4 times Ethyl l( i y xo-5-phenyl-lH- with ml. ofhydrochloric acid each time until no 1 ,4-benzodiazepinl -y] )methyl lcmore pyridine odor is to be perceived in the wash-water III- Ethyl l;5-( p eny )-2,3- 45 on treatment with alkali. The organic phase iswashed y A- p -y lwith a further 80 ml. of sodium bicarbonate solutionmethyucarbamate' and subsequently dried over sodium sulfate. After re-Toxicity Rotating Rod Pentamethylene-tetrazole Compound (DL (HD (APR2.0)

I 2500-5000 mg/kg. p.o. 5 mg/kg. p.o. 5.5 mg/kg. p.o. Iii 3388 Qiii:B38: 3 25%: $38: T3525: 33:

The compounds of formula I can be prepared in the moval of the ether,ethyl (N-methyl-N-pform of various pharmaceutical preparations whichtoluenesulphonyloxy)carbamate remains as a readily contain them or theirsalts in admixture with a pharmamobile colorless oil which rapidlycrystallizes. It is receutical, organic or inorganic inert carriermaterial 60 crystallized from ether/petroleum ether and then melts whichis suitable for enteral, percutaneous or parenat 4647. teral aplication. Suitable carrier materials for this purpose include water,gelatin, gum arabic, lactose, EXAMPLE 2 starches magnesium Steafateitalci Vegetable Oils, P According to the procedure described in Example1, alkylene glycols, Vaseline, etc. The pharmaceutical from 2.7 g. of7-chloro-l ,3-dihydro-5-phenyl-2H-l,4-

formulations can be prepared in solid form (e.g., as tablets, dragees,suppositories, capsules); in semi-solid form (e.g., as ointrnents); orin liquid form (e.g., as sobenzodiazepin-2-one, 4.5 g. of ethyl(N-methyl-N-ptoluenesulphonyloxy)carbamate, 10 ml. of dimethylformamideand 20 ml. of triethylamine there is obtained, after chromatography on150 g. of silica gel with 20 percent acetic ester in methylenechlorideand crystallization from ether/ hexane, ethyl [(7-chloro-2,3-

. dihydro-2-oxo-5-phenyllH-l ,4-benzodiazepinl yl)methyl]carbarnatewhich is recrystallized from methanol-water and then melts at l26129.

' EXAMPLE 3 EXAMPLE 4 A mixture of 2 g. of7-chloro-l,3-dihydro-5-phenyl- 2H- l,4 benzodiazepin-2-one, 4 g; ofethyl (N-benzyl- N-p-toluenesulphonyloxy)carbamate, 10 ml. ofdimethylformamide and 20 ml. of triethylamine is boiled under reflux for4 hours. The mixture is subsequently evaporated and the residuepartitioned between water and benzene. The benzene phase is washed withwater, dried over sodium sulfate and evaporated. The crude productremaining as the residue is chromatographed onv 150 g. of silica gelwith 10 percent ethyl acetate in methylene chloride. The pure fractionscrystallize from ether-hexane on standing in the refrigerator. Afterrecrystallization from ethanol, there is obtained ethyl [or-7-chloro-2,3-dihydro-2-oxo-5-phenyll H- l ,4-benzodiazepin-l-yl)benzyl]carbamate of melting point l77-l70. I

The ethyl (N-benzyl-N-p-toluenesulphonylOXy)Carbamate used as thestarting product can be manufactured as follows:

3 l .9 g. of benzylhydroxylamine hydrochloride are treated with 130 ml.of 3N caustic soda, whereby the free base precipitates. This isdissolved in 50 ml. of chloroform and, with ice-cooling and powerfulstirring, slowly treated dropwise at ca with 21.6 g. of chloroformicacid ethyl ester. After completed addition, the ice-bath is removed andthe mixture is further stirred at room temperature for a further 2hours. The chloroform phase is thereafter separated off; the aqueousphase is saturated with sodium chloride and extracted with ether. Thecombined organic phases are dried over sodium sulfate. After evaporatingoff the solvent, N-benzyl-N-carbethoxyhydroxylamine remains as a paleorange-colored oil which is purified by distillation; v

boiling point l30/0.05 mm Hg.

. A solution of 19.5 g. of the above N-benzyl-N- carbethoxyhydroxylaminein 80 ml. of ether is underlayed with a solution of 5 g. of sodiumhydroxide in 80 ml. of water. A solution of 19 g. of p-toluenesulphonylchloride in 80 ml. of ether is thereupon slowly added dropwise withpowerful stirring and with ice-cooling. After completed addition, theice-bath is removed and the mixture is further stirred at roomtemperature for a further 2 hours. The two phases are then separated,the organic phase dried over sodium sulfate and the ether evaporatedoft. An orange oil remains which is dissolved in acetone andbrought tocrystallization at low temperature (ca -20). The ethyl(N-benzyl-N-ptoluenesulphonyloxy)carbamate melts at 38 -40.

' EXAMPLES A mixture of 10.8 g. of 7-chloro-1,3-dihydro-5-phenyl-2H-1,4benzodiazepin-2-one, .20 g. of crude ethyl(N-ethyl-N-p-toluenesulphonyloxy)carbamate, 40 ml. of dimethylformamideand ml. of triethylamine is boiled under reflux for 4 hours. Afterevaporation in vacuum, the residue is partitioned between benzene andwater. The benzene phase is washed with water, dried over sodium sulfateand evaporated. Crystallization of the residue from methylenechloride/ether gives back the unreacted starting material. The motherliquor is evaporated. By chromatography of the residue on 250 g. ofsilica gel with 20% ethyl acetate in methylene chloride, there isobtained, after crystallization from ethanol, pure ethyl[1-(7-ch1oro-2,3 dihydro-2- oxo-S-phenyl- 1 H- 1 ,4-benzodiazepin- 1-yl)ethyl carbamate of melting point l57.

The ethyl (N-ethyl-N-p-toluenesulphonyloxy)carbamate used as thestarting product is manufactured in accordance with the data in Examples1 and 4 from N- ethyl-N-carbethoxyhydroxylamine and ptoluenesulphonylchloride and is further processed as the crude. product without priorpurification.

EXAMPLE 6 An aqueous solution of l I g. of 2-amino-N-(ethoxycarbonylamino )methyl ]-2'-benzoyl-4 chloroacetanilidehydrochloride is made alkaline with 10 percent sodium carbonatesolution. The base precipitated is extracted with methylene chloride.The extracts are dried over sodium sulfate and evaporated. The residueis taken up in ethanol and the solution obtained is boiled under refluxfor 10 minutes. The crude productwhich remains as the residue afterevaporation of the solution is crystallized from methanol/water. Ethyl(7chloro-2,3-dihydro-2-oxo-5-phenyll H- l ,4-benzodiazepin-l-yl)methyl]carbamate of melting point l242l6 is obtained.

The 2-amino-N-[(ethoxycarbonylamino)methyl1-2benzoyl-4-chloroacetanilide hydrochloride used as the starting productcan be manufactured as follows:

' 8.4 g of 2'-benzoyl-2-benzyloxycarbonylamino-4- chloroacetanilide. and9 gof ethyl (N-methyl-N-ptoluenesulphonyloxy)carbamate are boiled underreflux for 3 hours in a mixture of 20 ml of dimethylformamide and 40 m1of triethylamine. The reaction mixture is concentrated and thenpartitioned between water and ether. The ether phase is washed withwater, dried over sodium sulphate and evaporated. Chromatography of theresidue on 200 g of silica gel with 20 percent ethyl acetate inmethylene chloride yields, besides unreacted starting material, pure N-[(ethoxycarbonylamino)methyl]-2'-benzyl-2-benzyloxycarbonylamino-4-chloroacetanilide as a colorless resin.

2.1 g of the above (ethoxycarbonylami no )methyl ]-2 '-benzoyl-2-benzyloxycarbonylamino-4-chloroacetanilide are hydrogenated for 45minutes in 30 ml of ethanol in the presence of 0.5 g of palladiumcatalyst (5 percent on charcoal) and 5 'r'nmol of hydrogen chloride. Themixture is thereupon filtered off the catalyst and concentratedin vacuumat 20-30. Z-Amino-N- (ethoxycarbonylamino )methyl 2 '-benzoyl-4'-chloroacetanilide hydrochloride precipitates as a resin decanted off andthe residue stirred up with ether. The amorphous powder which isobtained on filtering off by suction is washed with ether and dried invacuum. There is obtained an almost colorless product, the aqueoussolution of which displays a pH of ca 4-5.

EXAMPLE 7 chlorobenzoyl )acetanilide hydrochloride);

ethyl [a-(7-chloro-2,3-dihydro-2-oxo-S-phenyl-1H- l ,4-benzodiazepinl-yl )benzyl ]carbamate, melting point l77l79 after crystallization fromethanol (from 2-amino-N-[a-(ethoxycarbonylamino)benzyll-2'-benzoyl-4'-chloroacetanilide hydrochloride;

ethyl 1-(7-chloro-2,3-dihydro-2-oxo-5-phenyl-lH- l ,4-benzodiazepinl -yl)ethyl ]carbamate, melting point l55l57 after crystallization fromethanol (from 2- amino-N-[ l-(ethoxycarbonylamino)ethyl ]-2-benzoyl-4'-chloroacetanilide hydrochloride).

EXAMPLE 8 Tablets of the following composition are manufactured:

per tablet Ethyl [(2.34iihydro-7-nitrodiazepinl-yl)methyl]carbamate 10mg Corn starch 53 mg Lactose 150 mg Gelatin ltWr solution) 6 mg Theactive substance, the corn starch and the lactose are mixed with a 10percent gelatin solution. The paste is comminuted and the granulatedried in a suitable pan at 43. The dried granulate is conducted througha comminuting machine and mixed with the following ingredients in amixer:

Talc 6 mg Magnesium stearate 6 mg Cron starch 9 mg The mixture isthereupon compressed to tablets of 450 mg.

EXAMPLE 9 Suppositories are manufactured with the following ingredients:

gr [.3 g supwsitog Ethyl [52,3-dihydro-7-nitro- 2 oxo- -phen l-lH-l4-benzodiazepm-l-yl methyllcarbamate 0.025 g Cocoa butter smelting point36- 7) 1.230 g Camauba wax 0.045 g Cocoa butter and carnauba wax aremelted, well mixed and cooled to 45. The well comminuted activeingredient is thereupon added and stirred until distribution is completeand uniform. The mixture is poured into suppository moulds which ensurea suppository weight of 1.3 g. After cooling, the suppositories aretaken from the moulds and individually wrapped in wax paper or metalfoil.

EXAMPLE 10 A parenteral formulation is manufactured with the followingingredients:

er ml. Ethyl 5 mg. LS3,3-dihydro-7-nitro-2-oxo-5- henyll H- l ,4-

nzodiazepinl yl )methyl1car amate Dimet'iylace de Propy ene Benzy alcoEthanol Water for In ection q.s. ad

tami lycol The active substance is dissolved in the dimethylacetamide,benzyl alcohol, propylene glycol, ethanol and water are added, themixture 18 filtered through a candle filter and the filtrate is filledinto ampules of a suitable size. The ampules are thereupon sealed andsterilized.

EXAMPLE 1 1 Tablets and suppositories and a parenteral formulation aremanufactured according to the processes described in Examples 8 to 10,but ethyl [(7-chlor0-2,3- dihydro-Z-oxo-S-phenyll H- l,4-benzodiazepin-1- yl)methyl]carbamate or ethyl [7-chloro-5-(2-chlorophenyl )-2,3-dihydro-2-oxol l-ll ,4-benzodiazepin-l-yHmethyllcarbamate is used as the active substance.

We claim:

1. A compound of the formula wherein R signifies hydrogen, lower alkylor aryl selected from the group consisting of phenyl, halo substitutedphenyl and lower alkyl substituted phenyl; R signifies lower alkyl and Ris aryl selected from the group consistin of phenyl, halo substitutedphenyl and lower a yl substituted phenyl.

2. The compound of claim 1 wherein R is hydrogen, R is ethyl and R isp-tolyl, i.e., a compound of the formula ethyl(N-methyl-N-p-toluenesulfonyloxy)carbamate.

3. The compound of claim 1 wherein R is phenyl, R is ethyl and R isp-tolyl, i.e., a compound of the formula ethyl(N-benzyl-N-p-toluenesulfonyloxy)carbamate.

4. The compound of claim 1 wherein R is methyl; R is ethyl and R isp-tolyl, i.e., a compound of the formula ethyl(N-ethyl-N-p-toluenesulfonyloxy)carbamate.

1. A COMPOUND OF THE FORMULA
 2. The compound of claim 1 wherein R3 ishydrogen, R4 is ethyl and R5 is p-tolyl, i.e., a compound of the formulaethyl (N-methyl-N-p-toluenesulfonyloxy)carbamate.
 3. The compound ofclaim 1 wherein R3 is phenyl, R4 is ethyl and R5 is p-tolyl, i.e., acompound of the formula ethyl(N-benzyl-N-p-toluenesulfonyloxy)carbamate.
 4. The compound of claim 1wherein R3 is methyl; R4 is ethyl and R5 is p-tolyl, i.e., a compound ofthe formula ethyl (N-ethyl-N-p-toluenesulfonyloxy)carbamate.